Tissue Transglutaminase Antibodies  | Anti-Gliadin Antibodies  |
Parietal Cell Antibodies  | Helicobacter Pylori Antibodies 

Tissue Transglutaminase Antibodies

Promotion Material

Performance Characteristics
EliA Celikey (anti-tTG), Gliadin (pdf)

Antigens

Tissue transglutaminase belongs to a diverse family of calcium-dependent enzymes that catalyze cross-link formation between proteins. tTG is widely distributed in human organs and is found associated with fibres surrounding smooth muscle and endothelias cells in connective tissue. tTG plays a role in extracellular matrix assembly and tissue repair mechanisms. Wheat gliadins can act as a substrate for the transglutaminase reactions.

Celikey uses human, recombinant tissue transglutaminase, produced in eukaryotic cells (Baculovirus/Sf9 system). 

Disease association, antibody prevalence and specificity

Celiac Disease

• Clinical sensitivity: 96%
• Clinical specificity: 99%

Disease activity

Anti-tissue transglutaminase antibodies may have a place in monitoring dietary compliance, with titres being negative in more than 70% of treated patients with celiac disease.

Information about the disease

When is the measurement recommended?

Suspicion of Celiac Disease

Antibody isotype

IgA or IgG.

IgA-deficiency is a special challenge in celiac disease diagnostics. IgG anti-tTG antibodies are as characteristic for celiac patients with IgA deficiency as IgA class anti-tTG antibodies for patients with normal serum IgA values.

References

• Mäki M, Collin P (1997) Coeliac disease. Lancet 349, 1755-1759 
• Brusco G, Muzi P, Ciccocioppo R, et al. (1999) Transglutaminase and coeliac disease: endomysial reactivity and small bowel expression. Clin Exp Immunol 118, 371-375 
• Troncone R, Maurano F, Rossi M, et al. (1999) IgA antibodies to tissue transglutaminase: An effective diagnostic test for celiac disease. J Pediatr 134, 166-171 
• Hansson T, Dahlbom I, Hall J, et al. (2000) Antibody reactivity against human and guinea pig tissue transglutaminase in children with celiac disease. J Pediatr Gastroenterol Nutr 30, 379-384

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Anti-Gliadin Antibodies

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Promotion Material

Performance Characteristics
EliA Celikey (anti-tTG), Gliadin (pdf)

Antigens

The term "gluten" comprises a whole series of proteins in the endosperm of the cereal genera of wheat, rye, barley and oats. They serve as a source of nitrogen for the germinating embry and are subclassified as albumins, globulins, glutelins and the celiac disease inducing gliadins. Gliadin (molecular weight 16-40 kDa) is a mixture of about 50 components. On the basis of electrophoretic mobility, gliadins can be devided into four major fractions: alpha-, beta-, gamma- and omega-gliadins. A-gliadin is a component of alpha-gliadin of known primary amino acid sequence contains 32 glutamines and 15 prolines per 100 amino acid residues.

The Varelisa Gliadin Antibodies assays are coated with purified gliadin. 

Deamidated Gliadin Peptides

Recent research revealed that gliadin peptides crossing the mucosal border in CD patients are deamidated by tissue transglutaminase (tTG), which renders them much more immunogenic than unprocessed gliadin peptides. Thus, deamidated gliadin peptides represent more specific targets for the antibodies to gliadin which are produced in CD patients. 

The EliA Gliadin DP tests use the relevant synthetic deamidated gliadin peptides which gives them an excellent specificity. 

Disease association, antibody prevalence and specificity

• Celiac disease = gluten-sensitive enteropathy (85-100% of children with celiac disease during the active phase of the disease) 
• Other gastroenterological disorders (about 21% IgG, about 3% IgA)

Information about the disease

Disease activity

When gluten is withdrawn from the diet of the patient with celiac disease, the IgA-AGA titer decreases rapidly to normal values while the IgG-AGA decreases slowly and may persist at low titer for months or years. During a diagnostic gluten challenge, both IgG and IgA-AGA usually reach pathological values after some weeks or months of gluten ingestion. 

When is the measurement recommended?

• Suspicion of Celiac Disease 
• Differential diagnosis of childhood and adult forms of Celiac Disease 
• Follow-up of gluten-free diets 
• Suspicion of Dermatitis Herpetiformis

Antibody isotypes

IgA and IgG. IgA is more specific but less sensitive, IgG is sensitive but less specific, thus the determination of both isotypes is usually recommended. Patients with selective IgA deficiency can only be detected by screening with an IgG class antibody.

References

• Mäki M, Collin P (1997) Coeliac disease. Lancet 349, 1755-1759 
• Catassi C (1996) Gliadin antibodies. In: Peter JB, Shoenfeld Y (eds.) Autoantibodies, pp 285-290, Elsevier, Amsterdam 
• Unsworth DJ (2000) Antiendomysial and antigliadin antibody tests and diagnosis of celiac disease. Marsh MN (ed.) Celiac Disease: Methods and Protocols [41], 247-255. Methods in molecular medicine, Humana Press Inc., Totowa, USA 
• Troncone R, Ferguson A (1991) Anti-gliadin antibodies. J Pediatr Gastroenterol Nutr 12, 150-148

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Parietal Cell Antibodies

Antigens

Circulating autoantibodies to gastric parietal cells were first detected in patients with pernicious anemia. Subsequent biochemical and molecular cloning studies identified the autoantigens as the alpha- and beta-subunits of the gastric H+/K+-ATPase (92 and 60-90 kDa, respectively). The membrane-bound gastric H+/K+-ATPase is a proton pump responsible for the acidification of the stomach lumen. It is localized to specialized intracellular and apical membranes of parietal cells of the gastric mucosa.

The Varelisa Parietal Cell Antibodies assay uses purified H+/K+-ATPase. 

Antibody specificity and prevalence

• Pernicious Anemia (55-90%) 
• Chronic Atrophic Gastritis type A 
• Autoimmune endocrine disorders such as Thyrotoxicosis, Hashimoto's Thyroiditis and insulin-dependent Diabetes Mellitus (20-30%) - in these cases high risk for type A gastric lesion 
• Healthy individuals (2-5%), increasing with age

Information about Pernicious Anemia

Disease activity

A correlation between autoantibody titer and severity of gastric atrophy is supported by one study but not by another. Treatment with corticoid drugs result in regeneration of gastric parietal cells, activities of parietal cell autoantibodies, however, showed no correlative change.

When is the measurement recommended?

• Suspicion of Pernicious Anemia 
• Differentiation of type A Atrophic Gastritis from the other forms of nonspecific histological gastritis (type B, Helicobacter pylori-associated gastritis, type AB, and reflux gastritis following surgery)

Antibody isotype

IgG

References

• Gleeson PA, van Driel IR, Toh B-H (1996) Parietal cell autoantibodies. In: Peter JB, Shoenfeld Y (eds.), Autoantibodies, pp 600-606, Elsevier, Amsterdam 
• Toh BH, Sentry JW, Alderuccio F (2000) The causative H+/K+ ATPase antigen in the pathogenesis of autoimmune gastritis. Immunol Today 21, 348 
• Klaasen CH, De Pont JJ (1994) Gastric H+/K+-ATPase. Cell Physiol Biochem 4, 115-134

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Helicobacter Pylori Antibodies

Antigens

The Varelisa Parietal Cell Antibodies assay uses purified H.pylori surface antigens and recombinant 120 kDa antigen. 

Antibody specificity and prevalence

The organism known as Helicobacter pylori was first discovered and reported in 1983 by Warren and Marshall. They reported a new gram-negative spiral bacterium found in gastric mucosa and associated with active, chronic gastritis. Meanwhile it is assumed that H. pylori causes chronic gastritis, is implicated as a major cause of gastric and duodenal ulcer disease and is recognized as a class I carcinogen for gastric cancer.

Studies have shown that H.pylori infection is ubiquitous, with approximately 50 % of the world's population estimated to be infected. The prevalence is higher in developing countries (up to 79 %) than in developed states.

Several “invasive” and "non-invasive" techniques have been described for diagnosing H.pylori infection. Of the invasive tests available, histology and the rapid urease tests are the most commonly used. Although these methods have very high positive predictive values, they require biopsies to be taken from the upper gastrointestinal tract. Commonly used non-invasive tests are the urea breath test that requires the ingestion of isotopically labeled urea and serological methods that determine serum antibodies to H. pylori.

When is the measurement recommended?

• Chronic Gastritis
• Duodenal Ulcer
• Suspicion of infection with H.pylori

Antibody isotype

IgG

References

• Warren JR, Marshall BJ. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983; 1:1273-1275
• Asaka M et al. Long-Term Helicobacter infection - from gastritis to gastric cancer. Aliment Pharmacol Therapeutics 1998; 12:9-15
• Azuma T et al. Diagnosis of Helicobacter pylori infection. J Gastroenterol Hepatol 1996; 11:662-669

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